A FUNCTIONAL SOLUBLE FORM OF THE MURINE MANNOSE RECEPTOR IS PRODUCED BY MACROPHAGES IN-VITRO AND IS PRESENT IN MOUSE SERUM

A soluble form of the mannose receptor (sMR) has been found in conditi oned medium of primary macrophages in vitro and in mouse serum, sMR wa s released as a single species, had a smaller size than the cell-assoc iated form, and accumulated in macrophage-conditioned medium, in a cyt okine-regulated manner, to levels comparable with those found for cell -associated mannose receptor. Pulse-chase experiments showed that sMR production in culture occurred by constitutive cleavage of pre-existin g full-length protein. A binding assay was developed to determine the sugar specificity of sMR and its ability to interact with pathogens an d particulate antigens (i.e. Candida albicans and zymosan). Protease i nhibitor studies suggested that sMR was produced by cleavage of an int act mannose receptor by a matrix metalloprotease or ADAM metalloprotea se. A role for sMR in the immune response is proposed based on its bin ding properties, regulation by cytokines, and the previous discovery o f putative ligands for the cysteine-rich domain of the mannose recepto r in lymph nodes and spleen.